Molecular dynamics simulation of co-adsorbed terpinen-4-ol and 1,8-cineole on skin bilayer: Surface coverage and composition effects

Abstract

Understanding the permeation mechanism of natural active compounds through human skin is crucial for advanced cosmetics and drug delivery. In the study, molecular dynamics simulations were used to investigate the structural and dynamical properties of 1,8-Cineole and Terpinen-4-ol (the two main components of tea tree oil) adsorbed on the skin surface. All simulations were performed using the GROMACS (5.0) molecular dynamics package. The skin layer was modeled as a membrane bilayer consisting of ceramides, cholesterol, and free fatty acid. These systems' structural and dynamical properties were characterized by radial distribution function (RDF), self-diffusion coefficient calculated by mean square displacement (MSD), surface tension, and snapshot inspections. It was found that when a single active compound adsorbed on the skin, the increase in surface coverage led to the increase in peak density in RDF for both 1,8- Cineole and Terpinen-4-ol. The self-diffusion coefficient decreased monotonically for 1,8 – Cineole; however, the corresponding value for Terpinen-4-ol increased as surface coverage increased. When both 1.8-Cineole and Terpinen-4-ol were simultaneously adsorbed on the skin, the lowest self-diffusion coefficient and smallest surface tension reduction can be obtained simultaneously at a certain composition value. This study's results can also contribute to the theoretical basis of the special relationship between the ratio composition of the two main active ingredients in tea tree oil (1.8-Cineole and Terpinen-4-ol) on the ability to diffuse and adsorb on the skin surface.